The net-like, violaceous pattern on the infant’s skin was characteristic of livedo reticularis.

Livedo reticularis is thought to arise from a change in underlying cutaneous blood flow.¹ The appearance of this condition reflects the configuration of underlying cutaneous vasculature. Arterioles oriented perpendicularly to the skin can surface from a network where blood flows from arteriole to capillary to venule. The reticular appearance is a result of increased visibility of the venous plexus.¹

Common culprits of this manifestation are impaired arteriolar perfusion and venous congestion, which may be caused by vasospasm, arterial thrombosis, or hyperviscosity.¹ If diagnostic biopsies are needed, they should be taken from the pale central areas.

Livedo reticularis can be categorized into groups to help delineate the patient-specific pathogenesis: idiopathic, primary, secondary (due to underlying disease; see below), and physiologic.¹ Physiologic livedo reticularis, which this patient had, is known as cutis marmorata (CM); it occurs in response to cold temperatures. It may be more common, or visible, in individuals with lighter skin types and in preterm infants. The condition typically affects the lower extremities but may also occur on the trunk and upper extremities.¹

Physiologic livedo reticularis usually resolves with warming of the extremities. Secondary livedo reticularis usually manifests in older patients and is due to serious conditions such as malignancies, antiphospholipid syndrome, and Sneddon syndrome. For these patients, coagulopathy and malignancy evaluation targeting the underlying cause of the livedo reticularis is warranted. Interestingly, livedo reticularis may also be associated with COVID-19, but this association has not been reported frequently in children.²

The infant in this case experienced rapid resolution with warming. The family was educated about the CM form of livedo reticularis and instructed to keep her warm. No other treatment or evaluation was indicated.

‌

Photo courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of Christy Nwankwo, BA, University of Missouri-Kansas City School of Medicine and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The net-like, violaceous pattern on the infant’s skin was characteristic of livedo reticularis.

Livedo reticularis is thought to arise from a change in underlying cutaneous blood flow.¹ The appearance of this condition reflects the configuration of underlying cutaneous vasculature. Arterioles oriented perpendicularly to the skin can surface from a network where blood flows from arteriole to capillary to venule. The reticular appearance is a result of increased visibility of the venous plexus.¹

Common culprits of this manifestation are impaired arteriolar perfusion and venous congestion, which may be caused by vasospasm, arterial thrombosis, or hyperviscosity.¹ If diagnostic biopsies are needed, they should be taken from the pale central areas.

Livedo reticularis can be categorized into groups to help delineate the patient-specific pathogenesis: idiopathic, primary, secondary (due to underlying disease; see below), and physiologic.¹ Physiologic livedo reticularis, which this patient had, is known as cutis marmorata (CM); it occurs in response to cold temperatures. It may be more common, or visible, in individuals with lighter skin types and in preterm infants. The condition typically affects the lower extremities but may also occur on the trunk and upper extremities.¹

Physiologic livedo reticularis usually resolves with warming of the extremities. Secondary livedo reticularis usually manifests in older patients and is due to serious conditions such as malignancies, antiphospholipid syndrome, and Sneddon syndrome. For these patients, coagulopathy and malignancy evaluation targeting the underlying cause of the livedo reticularis is warranted. Interestingly, livedo reticularis may also be associated with COVID-19, but this association has not been reported frequently in children.²

The infant in this case experienced rapid resolution with warming. The family was educated about the CM form of livedo reticularis and instructed to keep her warm. No other treatment or evaluation was indicated.

‌

Photo courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of Christy Nwankwo, BA, University of Missouri-Kansas City School of Medicine and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The net-like, violaceous pattern on the infant’s skin was characteristic of livedo reticularis.

Livedo reticularis is thought to arise from a change in underlying cutaneous blood flow.¹ The appearance of this condition reflects the configuration of underlying cutaneous vasculature. Arterioles oriented perpendicularly to the skin can surface from a network where blood flows from arteriole to capillary to venule. The reticular appearance is a result of increased visibility of the venous plexus.¹

Common culprits of this manifestation are impaired arteriolar perfusion and venous congestion, which may be caused by vasospasm, arterial thrombosis, or hyperviscosity.¹ If diagnostic biopsies are needed, they should be taken from the pale central areas.

Livedo reticularis can be categorized into groups to help delineate the patient-specific pathogenesis: idiopathic, primary, secondary (due to underlying disease; see below), and physiologic.¹ Physiologic livedo reticularis, which this patient had, is known as cutis marmorata (CM); it occurs in response to cold temperatures. It may be more common, or visible, in individuals with lighter skin types and in preterm infants. The condition typically affects the lower extremities but may also occur on the trunk and upper extremities.¹

Physiologic livedo reticularis usually resolves with warming of the extremities. Secondary livedo reticularis usually manifests in older patients and is due to serious conditions such as malignancies, antiphospholipid syndrome, and Sneddon syndrome. For these patients, coagulopathy and malignancy evaluation targeting the underlying cause of the livedo reticularis is warranted. Interestingly, livedo reticularis may also be associated with COVID-19, but this association has not been reported frequently in children.²

The infant in this case experienced rapid resolution with warming. The family was educated about the CM form of livedo reticularis and instructed to keep her warm. No other treatment or evaluation was indicated.

‌

Photo courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of Christy Nwankwo, BA, University of Missouri-Kansas City School of Medicine and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

A long-standing request to clarify data irregularities in a 2021 ISCHEMIA substudy resulted in the publication of one correction, with a second correction in the works.

Further, the lone cardiac surgeon on the ISCHEMIA trial steering committee, T. Bruce Ferguson, MD, has resigned from the committee, citing a series of factors, including an inability to reconcile data in the substudy and two additional ISCHEMIA papers currently under review.

As previously reported, cardiac surgeons Faisal Bakaeen, MD, and Joseph Sabik III, MD, notified the journal Circulation in March that the Dr. Reynolds et al. substudy had inconsistencies between data in the main paper and supplemental tables detailing patients’ coronary artery disease (CAD) and ischemia severity.

The substudy found that CAD severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the landmark trial.

Circulation published a correction for the substudy on May 20, explaining that a “formatting error” resulted in data being incorrectly presented in two supplemental tables. It does not mention the surgeons’ letter to the editor, which can be found by clicking the “Q” icon below the paper.

Dr. Bakaeen, from the Cleveland Clinic, and Dr. Sabik, from University Hospitals Cleveland Medical Center, told this news organization that they submitted a second letter to editor on May 23 stating that “significant discrepancies” persist.

For example, 7.2% of participants (179/2,475) had moderate stenosis in one coronary vessel in the corrected Reynolds paper (Supplemental Tables I and II) versus 23.3% (697/2,986) in the primary ISCHEMIA manuscript published  in the New England Journal of Medicine (Table S5).

The number of patients with left main ≥ 50% stenosis is, surprisingly, identical in both manuscripts, at 40, they said, despite the denominator dropping from 3,845 participants in the primary study to 2,475 participants with an evaluable modified Duke Prognostic Index score in the substudy.

The number of participants with previous coronary artery bypass surgery (CABG) is also hard to reconcile between manuscripts and, importantly, the substudy doesn’t distinguish between lesions bypassed with patent grafts and unbypassed grafts or those with occluded grafts.

“The fact that the authors are working on a second correction is appreciated, but with such numerous inconsistencies, at some point you reach the conclusion that an independent review of the data is the right thing to do for such a high-profile study that received over $100 million of National Institutes of Health support,” Dr. Bakaeen said. “No one should be satisfied or happy if there is any shadow of doubt here regarding the accuracy of the data.”

Speaking to this news organization prior to the first correction, lead substudy author Harmony Reynolds, MD, NYU Langone Health, detailed in depth how the formatting glitch inadvertently upgraded the number of diseased vessels and lesion severity in two supplemental tables.

The bigger issue

Importantly, the recent AHA/ACC/SCAI coronary revascularization guidelines used ISCHEMIA data to support downgrading the CABG recommendation from class 1 to class 2B in 3-vessel CAD with normal left ventricular function and from class 1 to 2a in 3-vessel CAD with mild to moderate left ventricular dysfunction.

The trial reported no significant benefit with an initial invasive strategy over medical therapy in stable patients with moderate or severe CAD. European guidelines, however, give CABG a class I recommendation for severe three- or two-vessel disease with proximal left anterior descending (LAD) involvement.

Dr. Sabik and Dr. Bakaeen say patients with severe three- or two-vessel disease with proximal LAD involvement were underrepresented in the randomized trials cited by the guidelines but are the typical CABG patients in modern-day practice.

“That is why it is important to determine the severity of CAD accurately and definitively in ISCHEMIA,” Dr. Bakaeen said. “But the more we look at the data, the more errors we encounter.”

Two U.S. surgical groups that were part of the writing process withdrew support for the revascularization guidelines, as did several international surgical societies, citing the data used to support the changes as well as the makeup of the writing committee.

Dr. Ferguson, now with the medical device manufacturer Perfusio, said he resigned from the ISCHEMIA steering committee on May 8 after being unable to accurately reconcile the ISCHEMIA surgical subset data with the Reynolds substudy and two other ISCHEMIA papers on the CABG subset. At least one of those papers, he noted, was being hurriedly pushed through the review process to counter concerns raised by surgeons regarding interpretation of ISCHEMIA.

“This is the first time in my lengthy career in medicine where a level of political agendaism was actually driving the truck,” he said. “It was appalling to me, and I would have said that if I was an interventional cardiologist looking at the results.”

ISCHEMIA results have also been touted as representing state-of-the-art care around the world, but that didn’t appear to be the case for the surgical subset where, for example, China and India performed most CABGs off pump, and globally there was considerable variation in how surgeons approached surgical revascularization strategies, Dr. Ferguson said. “Whether this variability might impact the guideline discussion and these papers coming out remains to be determined.”

He noted that the study protocol allowed for the ISCHEMIA investigators to evaluate whether the variability in the surgical subset influenced the results by comparing the data to that in the Society of Thoracic Surgeons registry, but this option was never acted upon despite being brought to their attention.

“Something political between 2020 and 2022 has crept into the ISCHEMIA trial mindset gestalt, and I don’t like it,” Dr. Ferguson said. “And this can have enormous consequences.”

Asked whether their letters to Circulation are being used to undermine confidence in the ISCHEMIA findings, Dr. Sabik replied, “It is not about undermining ISCHEMIA, but understanding how applicable ISCHEMIA is to patients having CABG today. Understanding the severity of the CAD in patients enrolled in ISCHEMIA is, therefore, necessary.”

“The authors and Circulation have admitted to errors,” he said. “We want to be sure we understand how severe the errors are.”

“This is just about accuracy in a manuscript that may affect patient treatment and therefore patient lives. We want to make sure it is correct,” Dr. Sabik added.

A version of this article first appeared on Medscape.com.

A long-standing request to clarify data irregularities in a 2021 ISCHEMIA substudy resulted in the publication of one correction, with a second correction in the works.

Further, the lone cardiac surgeon on the ISCHEMIA trial steering committee, T. Bruce Ferguson, MD, has resigned from the committee, citing a series of factors, including an inability to reconcile data in the substudy and two additional ISCHEMIA papers currently under review.

As previously reported, cardiac surgeons Faisal Bakaeen, MD, and Joseph Sabik III, MD, notified the journal Circulation in March that the Dr. Reynolds et al. substudy had inconsistencies between data in the main paper and supplemental tables detailing patients’ coronary artery disease (CAD) and ischemia severity.

The substudy found that CAD severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the landmark trial.

Circulation published a correction for the substudy on May 20, explaining that a “formatting error” resulted in data being incorrectly presented in two supplemental tables. It does not mention the surgeons’ letter to the editor, which can be found by clicking the “Q” icon below the paper.

Dr. Bakaeen, from the Cleveland Clinic, and Dr. Sabik, from University Hospitals Cleveland Medical Center, told this news organization that they submitted a second letter to editor on May 23 stating that “significant discrepancies” persist.

For example, 7.2% of participants (179/2,475) had moderate stenosis in one coronary vessel in the corrected Reynolds paper (Supplemental Tables I and II) versus 23.3% (697/2,986) in the primary ISCHEMIA manuscript published  in the New England Journal of Medicine (Table S5).

The number of patients with left main ≥ 50% stenosis is, surprisingly, identical in both manuscripts, at 40, they said, despite the denominator dropping from 3,845 participants in the primary study to 2,475 participants with an evaluable modified Duke Prognostic Index score in the substudy.

The number of participants with previous coronary artery bypass surgery (CABG) is also hard to reconcile between manuscripts and, importantly, the substudy doesn’t distinguish between lesions bypassed with patent grafts and unbypassed grafts or those with occluded grafts.

“The fact that the authors are working on a second correction is appreciated, but with such numerous inconsistencies, at some point you reach the conclusion that an independent review of the data is the right thing to do for such a high-profile study that received over $100 million of National Institutes of Health support,” Dr. Bakaeen said. “No one should be satisfied or happy if there is any shadow of doubt here regarding the accuracy of the data.”

Speaking to this news organization prior to the first correction, lead substudy author Harmony Reynolds, MD, NYU Langone Health, detailed in depth how the formatting glitch inadvertently upgraded the number of diseased vessels and lesion severity in two supplemental tables.

The bigger issue

Importantly, the recent AHA/ACC/SCAI coronary revascularization guidelines used ISCHEMIA data to support downgrading the CABG recommendation from class 1 to class 2B in 3-vessel CAD with normal left ventricular function and from class 1 to 2a in 3-vessel CAD with mild to moderate left ventricular dysfunction.

The trial reported no significant benefit with an initial invasive strategy over medical therapy in stable patients with moderate or severe CAD. European guidelines, however, give CABG a class I recommendation for severe three- or two-vessel disease with proximal left anterior descending (LAD) involvement.

Dr. Sabik and Dr. Bakaeen say patients with severe three- or two-vessel disease with proximal LAD involvement were underrepresented in the randomized trials cited by the guidelines but are the typical CABG patients in modern-day practice.

“That is why it is important to determine the severity of CAD accurately and definitively in ISCHEMIA,” Dr. Bakaeen said. “But the more we look at the data, the more errors we encounter.”

Two U.S. surgical groups that were part of the writing process withdrew support for the revascularization guidelines, as did several international surgical societies, citing the data used to support the changes as well as the makeup of the writing committee.

Dr. Ferguson, now with the medical device manufacturer Perfusio, said he resigned from the ISCHEMIA steering committee on May 8 after being unable to accurately reconcile the ISCHEMIA surgical subset data with the Reynolds substudy and two other ISCHEMIA papers on the CABG subset. At least one of those papers, he noted, was being hurriedly pushed through the review process to counter concerns raised by surgeons regarding interpretation of ISCHEMIA.

“This is the first time in my lengthy career in medicine where a level of political agendaism was actually driving the truck,” he said. “It was appalling to me, and I would have said that if I was an interventional cardiologist looking at the results.”

ISCHEMIA results have also been touted as representing state-of-the-art care around the world, but that didn’t appear to be the case for the surgical subset where, for example, China and India performed most CABGs off pump, and globally there was considerable variation in how surgeons approached surgical revascularization strategies, Dr. Ferguson said. “Whether this variability might impact the guideline discussion and these papers coming out remains to be determined.”

He noted that the study protocol allowed for the ISCHEMIA investigators to evaluate whether the variability in the surgical subset influenced the results by comparing the data to that in the Society of Thoracic Surgeons registry, but this option was never acted upon despite being brought to their attention.

“Something political between 2020 and 2022 has crept into the ISCHEMIA trial mindset gestalt, and I don’t like it,” Dr. Ferguson said. “And this can have enormous consequences.”

Asked whether their letters to Circulation are being used to undermine confidence in the ISCHEMIA findings, Dr. Sabik replied, “It is not about undermining ISCHEMIA, but understanding how applicable ISCHEMIA is to patients having CABG today. Understanding the severity of the CAD in patients enrolled in ISCHEMIA is, therefore, necessary.”

“The authors and Circulation have admitted to errors,” he said. “We want to be sure we understand how severe the errors are.”

“This is just about accuracy in a manuscript that may affect patient treatment and therefore patient lives. We want to make sure it is correct,” Dr. Sabik added.

A version of this article first appeared on Medscape.com.

A long-standing request to clarify data irregularities in a 2021 ISCHEMIA substudy resulted in the publication of one correction, with a second correction in the works.

Further, the lone cardiac surgeon on the ISCHEMIA trial steering committee, T. Bruce Ferguson, MD, has resigned from the committee, citing a series of factors, including an inability to reconcile data in the substudy and two additional ISCHEMIA papers currently under review.

As previously reported, cardiac surgeons Faisal Bakaeen, MD, and Joseph Sabik III, MD, notified the journal Circulation in March that the Dr. Reynolds et al. substudy had inconsistencies between data in the main paper and supplemental tables detailing patients’ coronary artery disease (CAD) and ischemia severity.

The substudy found that CAD severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the landmark trial.

Circulation published a correction for the substudy on May 20, explaining that a “formatting error” resulted in data being incorrectly presented in two supplemental tables. It does not mention the surgeons’ letter to the editor, which can be found by clicking the “Q” icon below the paper.

Dr. Bakaeen, from the Cleveland Clinic, and Dr. Sabik, from University Hospitals Cleveland Medical Center, told this news organization that they submitted a second letter to editor on May 23 stating that “significant discrepancies” persist.

For example, 7.2% of participants (179/2,475) had moderate stenosis in one coronary vessel in the corrected Reynolds paper (Supplemental Tables I and II) versus 23.3% (697/2,986) in the primary ISCHEMIA manuscript published  in the New England Journal of Medicine (Table S5).

The number of patients with left main ≥ 50% stenosis is, surprisingly, identical in both manuscripts, at 40, they said, despite the denominator dropping from 3,845 participants in the primary study to 2,475 participants with an evaluable modified Duke Prognostic Index score in the substudy.

The number of participants with previous coronary artery bypass surgery (CABG) is also hard to reconcile between manuscripts and, importantly, the substudy doesn’t distinguish between lesions bypassed with patent grafts and unbypassed grafts or those with occluded grafts.

“The fact that the authors are working on a second correction is appreciated, but with such numerous inconsistencies, at some point you reach the conclusion that an independent review of the data is the right thing to do for such a high-profile study that received over $100 million of National Institutes of Health support,” Dr. Bakaeen said. “No one should be satisfied or happy if there is any shadow of doubt here regarding the accuracy of the data.”

Speaking to this news organization prior to the first correction, lead substudy author Harmony Reynolds, MD, NYU Langone Health, detailed in depth how the formatting glitch inadvertently upgraded the number of diseased vessels and lesion severity in two supplemental tables.

The bigger issue

Importantly, the recent AHA/ACC/SCAI coronary revascularization guidelines used ISCHEMIA data to support downgrading the CABG recommendation from class 1 to class 2B in 3-vessel CAD with normal left ventricular function and from class 1 to 2a in 3-vessel CAD with mild to moderate left ventricular dysfunction.

The trial reported no significant benefit with an initial invasive strategy over medical therapy in stable patients with moderate or severe CAD. European guidelines, however, give CABG a class I recommendation for severe three- or two-vessel disease with proximal left anterior descending (LAD) involvement.

Dr. Sabik and Dr. Bakaeen say patients with severe three- or two-vessel disease with proximal LAD involvement were underrepresented in the randomized trials cited by the guidelines but are the typical CABG patients in modern-day practice.

“That is why it is important to determine the severity of CAD accurately and definitively in ISCHEMIA,” Dr. Bakaeen said. “But the more we look at the data, the more errors we encounter.”

Two U.S. surgical groups that were part of the writing process withdrew support for the revascularization guidelines, as did several international surgical societies, citing the data used to support the changes as well as the makeup of the writing committee.

Dr. Ferguson, now with the medical device manufacturer Perfusio, said he resigned from the ISCHEMIA steering committee on May 8 after being unable to accurately reconcile the ISCHEMIA surgical subset data with the Reynolds substudy and two other ISCHEMIA papers on the CABG subset. At least one of those papers, he noted, was being hurriedly pushed through the review process to counter concerns raised by surgeons regarding interpretation of ISCHEMIA.

“This is the first time in my lengthy career in medicine where a level of political agendaism was actually driving the truck,” he said. “It was appalling to me, and I would have said that if I was an interventional cardiologist looking at the results.”

ISCHEMIA results have also been touted as representing state-of-the-art care around the world, but that didn’t appear to be the case for the surgical subset where, for example, China and India performed most CABGs off pump, and globally there was considerable variation in how surgeons approached surgical revascularization strategies, Dr. Ferguson said. “Whether this variability might impact the guideline discussion and these papers coming out remains to be determined.”

He noted that the study protocol allowed for the ISCHEMIA investigators to evaluate whether the variability in the surgical subset influenced the results by comparing the data to that in the Society of Thoracic Surgeons registry, but this option was never acted upon despite being brought to their attention.

“Something political between 2020 and 2022 has crept into the ISCHEMIA trial mindset gestalt, and I don’t like it,” Dr. Ferguson said. “And this can have enormous consequences.”

Asked whether their letters to Circulation are being used to undermine confidence in the ISCHEMIA findings, Dr. Sabik replied, “It is not about undermining ISCHEMIA, but understanding how applicable ISCHEMIA is to patients having CABG today. Understanding the severity of the CAD in patients enrolled in ISCHEMIA is, therefore, necessary.”

“The authors and Circulation have admitted to errors,” he said. “We want to be sure we understand how severe the errors are.”

“This is just about accuracy in a manuscript that may affect patient treatment and therefore patient lives. We want to make sure it is correct,” Dr. Sabik added.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Patients with treatment-refractory schizophrenia in a long-term forensic facility showed significant stabilization following reduced doses of long-acting injectable antipsychotics, a study revealed.

“There is an argument by some experts in the field that state hospital populations represent a different set of patients who require higher antipsychotic dosages, with no alternative, but I don’t agree with that,” study lead author Mujeeb U. Shad, MD, GME-psychiatry program director and adjunct professor at the University of Nevada, Las Vegas, said in an interview.

In reducing doses, “patients appeared to blossom, becoming more active and less ‘zombie-like’; they started taking more interest in activities and their social [involvement] increased,” he said.

The study was among several presenting pros and cons of high antipsychotic doses at the 2022 annual meeting of the American Psychiatric Association.

Higher doses of antipsychotics are often relied upon when patients with acute psychosis fail to respond to standard treatment, however evidence supporting the approach is lacking.

And while some studies in fact show no benefit from the higher-dose maintenance therapy over conventional or even lower doses of antipsychotics, evidence regarding forensic patients hospitalized in long-term psychiatric facilities is also scant.

Meanwhile, the need to restore competency among those patients can be more pressing than normal.

“In a forensic population where executive cognitive function is one of the key elements to restore competency to stand trial, the continuation of high-dose therapy with excessive dopamine blockade may further compromise preexisting executive dysfunction to delay competency restoration,” Dr. Shad notes in the study.

The study describes a case series in which antipsychotic doses were lowered among 22 of Dr. Shad’s patients who had been determined to be incompetent to stand trial and referred to a state hospital to restore their competency.

With the objective of regaining the mental fitness to stand trial and being discharged from the facility, those on high doses of therapy, defined as a dose greater than 50% of the average package-insert dose, had their doses reduced to conventional dosages.

The approach led to as many as 68% of the patients being stabilized and discharged after having their competency restored, without symptom relapse, following an average antipsychotic dose reduction of 44%.

The average time to discharge following the dose reduction was just 2.3 months, after an average total hospitalization time of 11 months.

The shortest hospitalization durations (less than 7 months) were observed among those who did not receive changes in doses as they were already achieving efficacy with standard dosages.

Among two patients who were treated subtherapeutically, dose increases were required and they had the longest overall hospitalization (14.5 months)
 

Additional benefits of reduced dosages

Dr. Shad noted that, in addition to the earlier discharges, patients also had reductions in their polypharmacy, and in prolactin.

“We know that high prolactin level is such a huge problem, especially for female patients because it can cause osteoporosis, infertility, and abnormal menstruation, and the reductions in hyperprolactinemia can help reduce weight gain,” he said.

Dr. Shad added that he let some of those effects be his guide in making dose reductions.

“I was trying to gradually minimize the dose while monitoring the patients for relapse, and I used extrapyramidal symptoms and prolactin levels as my guide, looking for a sweet spot with the dosing,” he said.

“For example, if patients were taking an average of about 40-60 mg of a drug, I brought it down close to 20 mg, or close to the average package insert,” Dr. Shad said.

Key concerns among clinicians about reducing antipsychotic doses include the emergence of discontinuation or rebound symptoms, including psychosis, akathisia, or Parkinsonian symptoms, and studies, including a recent meta-analysis have supported those concerns, urging caution in reducing doses below standard levels.

However, Dr. Shad said his series suggests that reducing doses gradually while carefully monitoring extrapyramidal symptoms and prolactin levels may indeed pay off.

“They’re not the perfect guides, but they’re good guides, and with the right approach, [some] may be able to do this,” Dr. Shad said.

“However, the key to a successful dose reduction or discontinuation of an [antipsychotic medication] is to avoid abrupt discontinuation and follow a gradual dose reduction while monitoring symptoms and tolerability,” he said.

Commenting on the research, T. Scott Stroup, MD, a professor of psychiatry at Columbia University, New York, chimed in on the side of urging caution with higher doses and supporting possible benefits with the lower-dose approach.

“I agree that people who need antipsychotic medications should receive the lowest effective dose and that often this is identified by careful dose reduction,” he said in an interview.

Dr. Shad and Stroup had no disclosures to report.
 

NEW ORLEANS – Patients with treatment-refractory schizophrenia in a long-term forensic facility showed significant stabilization following reduced doses of long-acting injectable antipsychotics, a study revealed.

“There is an argument by some experts in the field that state hospital populations represent a different set of patients who require higher antipsychotic dosages, with no alternative, but I don’t agree with that,” study lead author Mujeeb U. Shad, MD, GME-psychiatry program director and adjunct professor at the University of Nevada, Las Vegas, said in an interview.

In reducing doses, “patients appeared to blossom, becoming more active and less ‘zombie-like’; they started taking more interest in activities and their social [involvement] increased,” he said.

The study was among several presenting pros and cons of high antipsychotic doses at the 2022 annual meeting of the American Psychiatric Association.

Higher doses of antipsychotics are often relied upon when patients with acute psychosis fail to respond to standard treatment, however evidence supporting the approach is lacking.

And while some studies in fact show no benefit from the higher-dose maintenance therapy over conventional or even lower doses of antipsychotics, evidence regarding forensic patients hospitalized in long-term psychiatric facilities is also scant.

Meanwhile, the need to restore competency among those patients can be more pressing than normal.

“In a forensic population where executive cognitive function is one of the key elements to restore competency to stand trial, the continuation of high-dose therapy with excessive dopamine blockade may further compromise preexisting executive dysfunction to delay competency restoration,” Dr. Shad notes in the study.

The study describes a case series in which antipsychotic doses were lowered among 22 of Dr. Shad’s patients who had been determined to be incompetent to stand trial and referred to a state hospital to restore their competency.

With the objective of regaining the mental fitness to stand trial and being discharged from the facility, those on high doses of therapy, defined as a dose greater than 50% of the average package-insert dose, had their doses reduced to conventional dosages.

The approach led to as many as 68% of the patients being stabilized and discharged after having their competency restored, without symptom relapse, following an average antipsychotic dose reduction of 44%.

The average time to discharge following the dose reduction was just 2.3 months, after an average total hospitalization time of 11 months.

The shortest hospitalization durations (less than 7 months) were observed among those who did not receive changes in doses as they were already achieving efficacy with standard dosages.

Among two patients who were treated subtherapeutically, dose increases were required and they had the longest overall hospitalization (14.5 months)
 

Additional benefits of reduced dosages

Dr. Shad noted that, in addition to the earlier discharges, patients also had reductions in their polypharmacy, and in prolactin.

“We know that high prolactin level is such a huge problem, especially for female patients because it can cause osteoporosis, infertility, and abnormal menstruation, and the reductions in hyperprolactinemia can help reduce weight gain,” he said.

Dr. Shad added that he let some of those effects be his guide in making dose reductions.

“I was trying to gradually minimize the dose while monitoring the patients for relapse, and I used extrapyramidal symptoms and prolactin levels as my guide, looking for a sweet spot with the dosing,” he said.

“For example, if patients were taking an average of about 40-60 mg of a drug, I brought it down close to 20 mg, or close to the average package insert,” Dr. Shad said.

Key concerns among clinicians about reducing antipsychotic doses include the emergence of discontinuation or rebound symptoms, including psychosis, akathisia, or Parkinsonian symptoms, and studies, including a recent meta-analysis have supported those concerns, urging caution in reducing doses below standard levels.

However, Dr. Shad said his series suggests that reducing doses gradually while carefully monitoring extrapyramidal symptoms and prolactin levels may indeed pay off.

“They’re not the perfect guides, but they’re good guides, and with the right approach, [some] may be able to do this,” Dr. Shad said.

“However, the key to a successful dose reduction or discontinuation of an [antipsychotic medication] is to avoid abrupt discontinuation and follow a gradual dose reduction while monitoring symptoms and tolerability,” he said.

Commenting on the research, T. Scott Stroup, MD, a professor of psychiatry at Columbia University, New York, chimed in on the side of urging caution with higher doses and supporting possible benefits with the lower-dose approach.

“I agree that people who need antipsychotic medications should receive the lowest effective dose and that often this is identified by careful dose reduction,” he said in an interview.

Dr. Shad and Stroup had no disclosures to report.
 

NEW ORLEANS – Patients with treatment-refractory schizophrenia in a long-term forensic facility showed significant stabilization following reduced doses of long-acting injectable antipsychotics, a study revealed.

“There is an argument by some experts in the field that state hospital populations represent a different set of patients who require higher antipsychotic dosages, with no alternative, but I don’t agree with that,” study lead author Mujeeb U. Shad, MD, GME-psychiatry program director and adjunct professor at the University of Nevada, Las Vegas, said in an interview.

In reducing doses, “patients appeared to blossom, becoming more active and less ‘zombie-like’; they started taking more interest in activities and their social [involvement] increased,” he said.

The study was among several presenting pros and cons of high antipsychotic doses at the 2022 annual meeting of the American Psychiatric Association.

Higher doses of antipsychotics are often relied upon when patients with acute psychosis fail to respond to standard treatment, however evidence supporting the approach is lacking.

And while some studies in fact show no benefit from the higher-dose maintenance therapy over conventional or even lower doses of antipsychotics, evidence regarding forensic patients hospitalized in long-term psychiatric facilities is also scant.

Meanwhile, the need to restore competency among those patients can be more pressing than normal.

“In a forensic population where executive cognitive function is one of the key elements to restore competency to stand trial, the continuation of high-dose therapy with excessive dopamine blockade may further compromise preexisting executive dysfunction to delay competency restoration,” Dr. Shad notes in the study.

The study describes a case series in which antipsychotic doses were lowered among 22 of Dr. Shad’s patients who had been determined to be incompetent to stand trial and referred to a state hospital to restore their competency.

With the objective of regaining the mental fitness to stand trial and being discharged from the facility, those on high doses of therapy, defined as a dose greater than 50% of the average package-insert dose, had their doses reduced to conventional dosages.

The approach led to as many as 68% of the patients being stabilized and discharged after having their competency restored, without symptom relapse, following an average antipsychotic dose reduction of 44%.

The average time to discharge following the dose reduction was just 2.3 months, after an average total hospitalization time of 11 months.

The shortest hospitalization durations (less than 7 months) were observed among those who did not receive changes in doses as they were already achieving efficacy with standard dosages.

Among two patients who were treated subtherapeutically, dose increases were required and they had the longest overall hospitalization (14.5 months)
 

Additional benefits of reduced dosages

Dr. Shad noted that, in addition to the earlier discharges, patients also had reductions in their polypharmacy, and in prolactin.

“We know that high prolactin level is such a huge problem, especially for female patients because it can cause osteoporosis, infertility, and abnormal menstruation, and the reductions in hyperprolactinemia can help reduce weight gain,” he said.

Dr. Shad added that he let some of those effects be his guide in making dose reductions.

“I was trying to gradually minimize the dose while monitoring the patients for relapse, and I used extrapyramidal symptoms and prolactin levels as my guide, looking for a sweet spot with the dosing,” he said.

“For example, if patients were taking an average of about 40-60 mg of a drug, I brought it down close to 20 mg, or close to the average package insert,” Dr. Shad said.

Key concerns among clinicians about reducing antipsychotic doses include the emergence of discontinuation or rebound symptoms, including psychosis, akathisia, or Parkinsonian symptoms, and studies, including a recent meta-analysis have supported those concerns, urging caution in reducing doses below standard levels.

However, Dr. Shad said his series suggests that reducing doses gradually while carefully monitoring extrapyramidal symptoms and prolactin levels may indeed pay off.

“They’re not the perfect guides, but they’re good guides, and with the right approach, [some] may be able to do this,” Dr. Shad said.

“However, the key to a successful dose reduction or discontinuation of an [antipsychotic medication] is to avoid abrupt discontinuation and follow a gradual dose reduction while monitoring symptoms and tolerability,” he said.

Commenting on the research, T. Scott Stroup, MD, a professor of psychiatry at Columbia University, New York, chimed in on the side of urging caution with higher doses and supporting possible benefits with the lower-dose approach.

“I agree that people who need antipsychotic medications should receive the lowest effective dose and that often this is identified by careful dose reduction,” he said in an interview.

Dr. Shad and Stroup had no disclosures to report.
 

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.

Women with polycystic ovary syndrome (PCOS) have an increased risk for several diseases and symptoms, many independent of body mass index (BMI), new research indicates.

Some diseases are linked for the first time to PCOS in this study, the authors wrote.

Researchers, led by Linda Kujanpää, MD, of the research unit for pediatrics, dermatology, clinical genetics, obstetrics, and gynecology at University of Oulu (Finland), found the morbidity risk is evident through the late reproductive years.

The paper was published online in Acta Obstetricia et Gynecologica Scandinavica.

This population-based follow-up study investigated comorbidities and medication and health care services use among women with PCOS in Finland at age 46 years via answers to a questionnaire.

The whole PCOS population (n = 280) consisted of women who reported both hirsutism and oligo/amenorrhea at age 31 (4.1%) and/or polycystic ovary morphology/PCOS at age 46 (3.1%), of which 246 replied to the 46-year questionnaire. They were compared with a control group of 1,573 women without PCOS.

Overall morbidity risk was 35% higher than for women without PCOS (risk ratio, 1.35; 95% confidence interval, 1.16-1.57). Medication use was 27% higher (RR, 1.27; 95% CI, 1.08-1.50), and the risk remained after adjusting for BMI.

Diagnoses with increased prevalence in women with PCOS were osteoarthritis, migraine, hypertension, tendinitis, and endometriosis. PCOS was also associated with autoimmune diseases and recurrent upper respiratory tract infections.

“BMI seems not to be solely responsible for the increased morbidity,” the researchers found. The average morbidity score of women with PCOS with a BMI of 25 kg/m² or higher was similar to that of women with PCOS and lower BMI.

Mindy Christianson, MD, medical director at Johns Hopkins Fertility Center and associate professor of gynecology and obstetrics at Johns Hopkins University, both in Baltimore, said in an interview that the links to diseases independent of BMI are interesting because there’s so much focus on counseling women with PCOS to lose weight.

While that message is still important, it’s important to realize that some related diseases and conditions – such as autoimmune diseases and migraine – are not driven by BMI.

“It really drives home the point that polycystic ovary syndrome is really a chronic medical condition and puts patients at risk for a number of health conditions,” she said. “Having a good primary care physician is important to help them with their overall health.”

Women with PCOS said their health was poor or very poor almost three times more often than did women in the control group.

Surprisingly few studies have looked at overall comorbidity in women with PCOS, the authors wrote.

“This should be of high priority given the high cost to society resulting from PCOS-related morbidity,” they added. As an example, they pointed out that PCOS-related type 2 diabetes alone costs an estimated $1.77 billion in the United States and £237 million ($310 million) each year in the United Kingdom.

Additionally, the focus in previous research has typically been on women in their early or mid-reproductive years, and morbidity burden data in late reproductive years are scarce.

The study population was pulled from the longitudinal Northern Finland Birth Cohort 1966 and included all pregnancies with estimated date of delivery during 1966 in two provinces of Finland (5,889 women).

Dr. Christianson said she hopes this study will spur more research on PCOS, which has been severely underfunded, especially in the United States.

Part of the reason for that is there is a limited number of subspecialists in the country who work with patients with PCOS and do research in the area. PCOS often gets lost in the research priorities of infertility, diabetes, and thyroid disease.

The message in this study that PCOS is not just a fertility issue or an obesity issue but an overall health issue with a substantial cost to the health system may help raise awareness, Dr. Christianson said.

This study was supported by grants from The Finnish Medical Foundation, The Academy of Finland, The Sigrid Juselius Foundation, The Finnish Cultural Foundation, The Jalmari and Rauha Ahokas Foundation, The Päivikki and Sakari Sohlberg Foundation, Genesis Research Trust, The Medical Research Council, University of Oulu, Oulu University Hospital, Ministry of Health and Social Affairs, National Institute for Health and Welfare, Regional Institute of Occupational Health, and the European Regional Development Fund. The Study authors and Dr. Christianson reported no relevant financial relationships.

Women with polycystic ovary syndrome (PCOS) have an increased risk for several diseases and symptoms, many independent of body mass index (BMI), new research indicates.

Some diseases are linked for the first time to PCOS in this study, the authors wrote.

Researchers, led by Linda Kujanpää, MD, of the research unit for pediatrics, dermatology, clinical genetics, obstetrics, and gynecology at University of Oulu (Finland), found the morbidity risk is evident through the late reproductive years.

The paper was published online in Acta Obstetricia et Gynecologica Scandinavica.

This population-based follow-up study investigated comorbidities and medication and health care services use among women with PCOS in Finland at age 46 years via answers to a questionnaire.

The whole PCOS population (n = 280) consisted of women who reported both hirsutism and oligo/amenorrhea at age 31 (4.1%) and/or polycystic ovary morphology/PCOS at age 46 (3.1%), of which 246 replied to the 46-year questionnaire. They were compared with a control group of 1,573 women without PCOS.

Overall morbidity risk was 35% higher than for women without PCOS (risk ratio, 1.35; 95% confidence interval, 1.16-1.57). Medication use was 27% higher (RR, 1.27; 95% CI, 1.08-1.50), and the risk remained after adjusting for BMI.

Diagnoses with increased prevalence in women with PCOS were osteoarthritis, migraine, hypertension, tendinitis, and endometriosis. PCOS was also associated with autoimmune diseases and recurrent upper respiratory tract infections.

“BMI seems not to be solely responsible for the increased morbidity,” the researchers found. The average morbidity score of women with PCOS with a BMI of 25 kg/m² or higher was similar to that of women with PCOS and lower BMI.

Mindy Christianson, MD, medical director at Johns Hopkins Fertility Center and associate professor of gynecology and obstetrics at Johns Hopkins University, both in Baltimore, said in an interview that the links to diseases independent of BMI are interesting because there’s so much focus on counseling women with PCOS to lose weight.

While that message is still important, it’s important to realize that some related diseases and conditions – such as autoimmune diseases and migraine – are not driven by BMI.

“It really drives home the point that polycystic ovary syndrome is really a chronic medical condition and puts patients at risk for a number of health conditions,” she said. “Having a good primary care physician is important to help them with their overall health.”

Women with PCOS said their health was poor or very poor almost three times more often than did women in the control group.

Surprisingly few studies have looked at overall comorbidity in women with PCOS, the authors wrote.

“This should be of high priority given the high cost to society resulting from PCOS-related morbidity,” they added. As an example, they pointed out that PCOS-related type 2 diabetes alone costs an estimated $1.77 billion in the United States and £237 million ($310 million) each year in the United Kingdom.

Additionally, the focus in previous research has typically been on women in their early or mid-reproductive years, and morbidity burden data in late reproductive years are scarce.

The study population was pulled from the longitudinal Northern Finland Birth Cohort 1966 and included all pregnancies with estimated date of delivery during 1966 in two provinces of Finland (5,889 women).

Dr. Christianson said she hopes this study will spur more research on PCOS, which has been severely underfunded, especially in the United States.

Part of the reason for that is there is a limited number of subspecialists in the country who work with patients with PCOS and do research in the area. PCOS often gets lost in the research priorities of infertility, diabetes, and thyroid disease.

The message in this study that PCOS is not just a fertility issue or an obesity issue but an overall health issue with a substantial cost to the health system may help raise awareness, Dr. Christianson said.

This study was supported by grants from The Finnish Medical Foundation, The Academy of Finland, The Sigrid Juselius Foundation, The Finnish Cultural Foundation, The Jalmari and Rauha Ahokas Foundation, The Päivikki and Sakari Sohlberg Foundation, Genesis Research Trust, The Medical Research Council, University of Oulu, Oulu University Hospital, Ministry of Health and Social Affairs, National Institute for Health and Welfare, Regional Institute of Occupational Health, and the European Regional Development Fund. The Study authors and Dr. Christianson reported no relevant financial relationships.

Women with polycystic ovary syndrome (PCOS) have an increased risk for several diseases and symptoms, many independent of body mass index (BMI), new research indicates.

Some diseases are linked for the first time to PCOS in this study, the authors wrote.

Researchers, led by Linda Kujanpää, MD, of the research unit for pediatrics, dermatology, clinical genetics, obstetrics, and gynecology at University of Oulu (Finland), found the morbidity risk is evident through the late reproductive years.

The paper was published online in Acta Obstetricia et Gynecologica Scandinavica.

This population-based follow-up study investigated comorbidities and medication and health care services use among women with PCOS in Finland at age 46 years via answers to a questionnaire.

The whole PCOS population (n = 280) consisted of women who reported both hirsutism and oligo/amenorrhea at age 31 (4.1%) and/or polycystic ovary morphology/PCOS at age 46 (3.1%), of which 246 replied to the 46-year questionnaire. They were compared with a control group of 1,573 women without PCOS.

Overall morbidity risk was 35% higher than for women without PCOS (risk ratio, 1.35; 95% confidence interval, 1.16-1.57). Medication use was 27% higher (RR, 1.27; 95% CI, 1.08-1.50), and the risk remained after adjusting for BMI.

Diagnoses with increased prevalence in women with PCOS were osteoarthritis, migraine, hypertension, tendinitis, and endometriosis. PCOS was also associated with autoimmune diseases and recurrent upper respiratory tract infections.

“BMI seems not to be solely responsible for the increased morbidity,” the researchers found. The average morbidity score of women with PCOS with a BMI of 25 kg/m² or higher was similar to that of women with PCOS and lower BMI.

Mindy Christianson, MD, medical director at Johns Hopkins Fertility Center and associate professor of gynecology and obstetrics at Johns Hopkins University, both in Baltimore, said in an interview that the links to diseases independent of BMI are interesting because there’s so much focus on counseling women with PCOS to lose weight.

While that message is still important, it’s important to realize that some related diseases and conditions – such as autoimmune diseases and migraine – are not driven by BMI.

“It really drives home the point that polycystic ovary syndrome is really a chronic medical condition and puts patients at risk for a number of health conditions,” she said. “Having a good primary care physician is important to help them with their overall health.”

Women with PCOS said their health was poor or very poor almost three times more often than did women in the control group.

Surprisingly few studies have looked at overall comorbidity in women with PCOS, the authors wrote.

“This should be of high priority given the high cost to society resulting from PCOS-related morbidity,” they added. As an example, they pointed out that PCOS-related type 2 diabetes alone costs an estimated $1.77 billion in the United States and £237 million ($310 million) each year in the United Kingdom.

Additionally, the focus in previous research has typically been on women in their early or mid-reproductive years, and morbidity burden data in late reproductive years are scarce.

The study population was pulled from the longitudinal Northern Finland Birth Cohort 1966 and included all pregnancies with estimated date of delivery during 1966 in two provinces of Finland (5,889 women).

Dr. Christianson said she hopes this study will spur more research on PCOS, which has been severely underfunded, especially in the United States.

Part of the reason for that is there is a limited number of subspecialists in the country who work with patients with PCOS and do research in the area. PCOS often gets lost in the research priorities of infertility, diabetes, and thyroid disease.

The message in this study that PCOS is not just a fertility issue or an obesity issue but an overall health issue with a substantial cost to the health system may help raise awareness, Dr. Christianson said.

This study was supported by grants from The Finnish Medical Foundation, The Academy of Finland, The Sigrid Juselius Foundation, The Finnish Cultural Foundation, The Jalmari and Rauha Ahokas Foundation, The Päivikki and Sakari Sohlberg Foundation, Genesis Research Trust, The Medical Research Council, University of Oulu, Oulu University Hospital, Ministry of Health and Social Affairs, National Institute for Health and Welfare, Regional Institute of Occupational Health, and the European Regional Development Fund. The Study authors and Dr. Christianson reported no relevant financial relationships.

SAN DIEGO – When Lacy M. Alexander, PhD, began her career as a kinesiology researcher, she focused on the skin as a model of circulation for examining mechanisms of vascular function and dysfunction in diseases, as well as the influence of drug interventions.

“The skin is an accessible circulation; we see many of the same neural and endothelial pathways mediating vasodilation that we see throughout the entire vascular system,” Dr. Alexander, professor of kinesiology at Penn State University’s College of Health and Human Development, University Park, Pa., said during a lecture at the annual meeting of the American College for Sports Medicine.

Doug Brunk/MDedge News

The main technique that she and other researchers use to examine microvascular endothelial function is intradermal microdialysis, which involves the placement of a thin catheter into the dermis. “This catheter has the ability to perfuse or infuse various substances into a bidirectional membrane,” Dr. Alexander explained. “This enables us to recover various substances into that catheter. We pair this with a measurement of skin blood flow with Doppler probes as well as the ability to control local temperature to either isolate reflex control of the human cutaneous circulation or elicit local changes in temperature to elicit vasodilation and vasoconstriction.”

In a 2005 article on evaluating the microcirculation in vascular disease, microvascular dysfunction is described as “a systemic disease process that occurs in a similar fashion in multiple tissue beds throughout the body”. Therefore, early identification of the mechanism leading to microvascular dysfunction is important, Dr. Alexander said. “We can also monitor the progression of disease and the progression of a given treatment if we have a noninvasive way to do that.”

A question that clinicians often ask Dr. Alexander is, do changes in forearm skin blood flow represent changes in, say, leg skin blood flow, or blood flow in other parts of the body? “The answer to that question is yes; we see similar changes in forearm skin that we see in other regions of the body,” she said. “We tend to use the forearm skin because there’s less UV damage, especially when we’re looking at questions related to human aging.”

Over the years, she and other investigators have used intradermal microdialysis to develop and refine many skin-specific approaches for examining endothelial function, including reactive hyperemia, direct drug delivery, local heating, whole body heating, local cooling, whole body cooling, and spectral analysis. For example, using this approach in the direct drug delivery realm, researchers have discovered that oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolemic middle-aged adults.

In more recent work using intradermal microdialysis, researchers have observed that peripheral microvascular function is impaired in adults with hypertension (Hypertension. 2017; 69[5]:902-9).

Another study using intradermal microdialysis found that 16 weeks of a sulfhydryl intervention improved endothelial function through nitric oxide and hydrogen sulfide-dependent mechanisms in adults with hypertension.

The technology has also helped to further understanding of nontraditional risk factors of microvascular dysfunction. In one study, researchers found that endothelium-dependent vasodilation is blunted in adults with major depressive disorder due to a reduced functional contribution of nitric oxide.

According to Dr. Alexander, a study being reviewed for publication found that microvascular endothelial function is impaired in women with endometriosis.

Also in 2019, a European Academy of Allergy and Clinical Immunology (EAACI) position paper on the use of intradermal microdialysis in investigations of the pathogenesis of chronic inflammatory skin diseases was published.

The broad focus of Dr. Alexander’s current projects includes examining the roles of arginase in nitric oxide synthase uncoupling in human vasculature with hypercholesterolemia and hypertension; inflammation-induced alteration in vasodilatory signaling with essential hypertension; the role of reactive oxygen species in altering vasoconstriction and vascular remodeling with hypertension, and the effects of common platelet inhibitors on microvascular function in human skin as they relate to basic mechanisms of skin blood flow and functional thermoregulatory outcomes. “The hope is that we can intervene with things like dietary and exercise interventions early on to mitigate this progression to avert cardiovascular disease,” she said.

Dr. Alexander disclosed that she has received research support from the National Heart, Lung, and Blood Institute, the National Dairy Council, the American College of Sports Medicine, and the American Heart Association.

SAN DIEGO – When Lacy M. Alexander, PhD, began her career as a kinesiology researcher, she focused on the skin as a model of circulation for examining mechanisms of vascular function and dysfunction in diseases, as well as the influence of drug interventions.

“The skin is an accessible circulation; we see many of the same neural and endothelial pathways mediating vasodilation that we see throughout the entire vascular system,” Dr. Alexander, professor of kinesiology at Penn State University’s College of Health and Human Development, University Park, Pa., said during a lecture at the annual meeting of the American College for Sports Medicine.

Doug Brunk/MDedge News

The main technique that she and other researchers use to examine microvascular endothelial function is intradermal microdialysis, which involves the placement of a thin catheter into the dermis. “This catheter has the ability to perfuse or infuse various substances into a bidirectional membrane,” Dr. Alexander explained. “This enables us to recover various substances into that catheter. We pair this with a measurement of skin blood flow with Doppler probes as well as the ability to control local temperature to either isolate reflex control of the human cutaneous circulation or elicit local changes in temperature to elicit vasodilation and vasoconstriction.”

In a 2005 article on evaluating the microcirculation in vascular disease, microvascular dysfunction is described as “a systemic disease process that occurs in a similar fashion in multiple tissue beds throughout the body”. Therefore, early identification of the mechanism leading to microvascular dysfunction is important, Dr. Alexander said. “We can also monitor the progression of disease and the progression of a given treatment if we have a noninvasive way to do that.”

A question that clinicians often ask Dr. Alexander is, do changes in forearm skin blood flow represent changes in, say, leg skin blood flow, or blood flow in other parts of the body? “The answer to that question is yes; we see similar changes in forearm skin that we see in other regions of the body,” she said. “We tend to use the forearm skin because there’s less UV damage, especially when we’re looking at questions related to human aging.”

Over the years, she and other investigators have used intradermal microdialysis to develop and refine many skin-specific approaches for examining endothelial function, including reactive hyperemia, direct drug delivery, local heating, whole body heating, local cooling, whole body cooling, and spectral analysis. For example, using this approach in the direct drug delivery realm, researchers have discovered that oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolemic middle-aged adults.

In more recent work using intradermal microdialysis, researchers have observed that peripheral microvascular function is impaired in adults with hypertension (Hypertension. 2017; 69[5]:902-9).

Another study using intradermal microdialysis found that 16 weeks of a sulfhydryl intervention improved endothelial function through nitric oxide and hydrogen sulfide-dependent mechanisms in adults with hypertension.

The technology has also helped to further understanding of nontraditional risk factors of microvascular dysfunction. In one study, researchers found that endothelium-dependent vasodilation is blunted in adults with major depressive disorder due to a reduced functional contribution of nitric oxide.

According to Dr. Alexander, a study being reviewed for publication found that microvascular endothelial function is impaired in women with endometriosis.

Also in 2019, a European Academy of Allergy and Clinical Immunology (EAACI) position paper on the use of intradermal microdialysis in investigations of the pathogenesis of chronic inflammatory skin diseases was published.

The broad focus of Dr. Alexander’s current projects includes examining the roles of arginase in nitric oxide synthase uncoupling in human vasculature with hypercholesterolemia and hypertension; inflammation-induced alteration in vasodilatory signaling with essential hypertension; the role of reactive oxygen species in altering vasoconstriction and vascular remodeling with hypertension, and the effects of common platelet inhibitors on microvascular function in human skin as they relate to basic mechanisms of skin blood flow and functional thermoregulatory outcomes. “The hope is that we can intervene with things like dietary and exercise interventions early on to mitigate this progression to avert cardiovascular disease,” she said.

Dr. Alexander disclosed that she has received research support from the National Heart, Lung, and Blood Institute, the National Dairy Council, the American College of Sports Medicine, and the American Heart Association.

SAN DIEGO – When Lacy M. Alexander, PhD, began her career as a kinesiology researcher, she focused on the skin as a model of circulation for examining mechanisms of vascular function and dysfunction in diseases, as well as the influence of drug interventions.

“The skin is an accessible circulation; we see many of the same neural and endothelial pathways mediating vasodilation that we see throughout the entire vascular system,” Dr. Alexander, professor of kinesiology at Penn State University’s College of Health and Human Development, University Park, Pa., said during a lecture at the annual meeting of the American College for Sports Medicine.

Doug Brunk/MDedge News

The main technique that she and other researchers use to examine microvascular endothelial function is intradermal microdialysis, which involves the placement of a thin catheter into the dermis. “This catheter has the ability to perfuse or infuse various substances into a bidirectional membrane,” Dr. Alexander explained. “This enables us to recover various substances into that catheter. We pair this with a measurement of skin blood flow with Doppler probes as well as the ability to control local temperature to either isolate reflex control of the human cutaneous circulation or elicit local changes in temperature to elicit vasodilation and vasoconstriction.”

In a 2005 article on evaluating the microcirculation in vascular disease, microvascular dysfunction is described as “a systemic disease process that occurs in a similar fashion in multiple tissue beds throughout the body”. Therefore, early identification of the mechanism leading to microvascular dysfunction is important, Dr. Alexander said. “We can also monitor the progression of disease and the progression of a given treatment if we have a noninvasive way to do that.”

A question that clinicians often ask Dr. Alexander is, do changes in forearm skin blood flow represent changes in, say, leg skin blood flow, or blood flow in other parts of the body? “The answer to that question is yes; we see similar changes in forearm skin that we see in other regions of the body,” she said. “We tend to use the forearm skin because there’s less UV damage, especially when we’re looking at questions related to human aging.”

Over the years, she and other investigators have used intradermal microdialysis to develop and refine many skin-specific approaches for examining endothelial function, including reactive hyperemia, direct drug delivery, local heating, whole body heating, local cooling, whole body cooling, and spectral analysis. For example, using this approach in the direct drug delivery realm, researchers have discovered that oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolemic middle-aged adults.

In more recent work using intradermal microdialysis, researchers have observed that peripheral microvascular function is impaired in adults with hypertension (Hypertension. 2017; 69[5]:902-9).

Another study using intradermal microdialysis found that 16 weeks of a sulfhydryl intervention improved endothelial function through nitric oxide and hydrogen sulfide-dependent mechanisms in adults with hypertension.

The technology has also helped to further understanding of nontraditional risk factors of microvascular dysfunction. In one study, researchers found that endothelium-dependent vasodilation is blunted in adults with major depressive disorder due to a reduced functional contribution of nitric oxide.

According to Dr. Alexander, a study being reviewed for publication found that microvascular endothelial function is impaired in women with endometriosis.

Also in 2019, a European Academy of Allergy and Clinical Immunology (EAACI) position paper on the use of intradermal microdialysis in investigations of the pathogenesis of chronic inflammatory skin diseases was published.

The broad focus of Dr. Alexander’s current projects includes examining the roles of arginase in nitric oxide synthase uncoupling in human vasculature with hypercholesterolemia and hypertension; inflammation-induced alteration in vasodilatory signaling with essential hypertension; the role of reactive oxygen species in altering vasoconstriction and vascular remodeling with hypertension, and the effects of common platelet inhibitors on microvascular function in human skin as they relate to basic mechanisms of skin blood flow and functional thermoregulatory outcomes. “The hope is that we can intervene with things like dietary and exercise interventions early on to mitigate this progression to avert cardiovascular disease,” she said.

Dr. Alexander disclosed that she has received research support from the National Heart, Lung, and Blood Institute, the National Dairy Council, the American College of Sports Medicine, and the American Heart Association.

Pregnant women with monkeypox will be advised to give birth by C-section to avoid infecting their baby during delivery, according to a new paper in Ultrasound in Obstetrics & Gynecology.

The risk of monkeypox infection remains low for the general public, the authors wrote, though cases continue to grow worldwide, particularly in the United Kingdom.

“We are aware infants and children are at greater risk of becoming seriously ill if they do catch monkeypox,” Edward Morris, MBBS, one of the authors and president of the Royal College of Obstetricians and Gynecologists, said in a statement.

“Therefore, to minimize the risk of a baby contracting the virus, we recommend health care professionals discuss the benefits and risks of having a cesarean birth with a pregnant woman or person who has or is suspected of having the virus,” he said.

Dr. Morris and colleagues pulled together existing evidence on monkeypox diagnosis, treatment, and recommended modes of birth for mothers and babies.

“The World Health Organization states there could be adverse consequences for pregnant women and babies if they become infected, including congenital monkeypox, miscarriage, or stillbirth, which is why we have provided clear guidance for health care professionals in this paper,” Dr. Morris said.

The monkeypox virus typically spreads through direct contact, droplets, or contaminated surfaces and objects. But some limited evidence shows that the virus can be passed from a mother to a baby via the placenta, which can lead to congenital monkeypox.

What’s more, mothers may be able to transmit the virus during or after birth. Although no evidence exists around the optimal mode of birth, a pregnant woman with an active monkeypox infection may choose to avoid vaginal delivery to reduce direct contact.

“If genital lesions are identified on a pregnant woman, then a cesarean birth will be recommended,” the authors wrote. “If a pregnant woman or person has suspected or confirmed monkeypox, a caesarean birth will be offered following discussion of the possible risk of neonatal infection, which may be serious.”

After giving birth, close contact can spread the virus as well. To minimize the risk, the authors recommend isolating the baby from family members who have confirmed or suspected monkeypox and carefully monitoring for infection.

Mothers with an active monkeypox infection should also avoid breastfeeding to lower the risk of spreading the virus to their newborn, the authors wrote. But to support breastfeeding after infection, mothers can express and discard milk until the isolation period has passed.

Pregnant women who become infected may also consider getting vaccinated, the authors wrote. Vaccination up to 14 days after exposure doesn’t prevent the disease but can reduce the severity of symptoms. In the current outbreak, public health organizations advised doctors to vaccinate contacts of confirmed cases, including pregnant people.

The data for monkeypox vaccine use in pregnant women is small, the authors wrote, including fewer than 300 women. In previous studies, no adverse outcomes were found. The vaccine is also considered safe for breastfeeding.

“The decision whether to have the vaccine in pregnancy should be a personal choice,” the authors wrote. “Pregnant women and people should be encouraged to discuss the risks and benefits of vaccination, including possible side effects, with a health care professional before making their final decision.”

A version of this article first appeared on Medscape.com.

Pregnant women with monkeypox will be advised to give birth by C-section to avoid infecting their baby during delivery, according to a new paper in Ultrasound in Obstetrics & Gynecology.

The risk of monkeypox infection remains low for the general public, the authors wrote, though cases continue to grow worldwide, particularly in the United Kingdom.

“We are aware infants and children are at greater risk of becoming seriously ill if they do catch monkeypox,” Edward Morris, MBBS, one of the authors and president of the Royal College of Obstetricians and Gynecologists, said in a statement.

“Therefore, to minimize the risk of a baby contracting the virus, we recommend health care professionals discuss the benefits and risks of having a cesarean birth with a pregnant woman or person who has or is suspected of having the virus,” he said.

Dr. Morris and colleagues pulled together existing evidence on monkeypox diagnosis, treatment, and recommended modes of birth for mothers and babies.

“The World Health Organization states there could be adverse consequences for pregnant women and babies if they become infected, including congenital monkeypox, miscarriage, or stillbirth, which is why we have provided clear guidance for health care professionals in this paper,” Dr. Morris said.

The monkeypox virus typically spreads through direct contact, droplets, or contaminated surfaces and objects. But some limited evidence shows that the virus can be passed from a mother to a baby via the placenta, which can lead to congenital monkeypox.

What’s more, mothers may be able to transmit the virus during or after birth. Although no evidence exists around the optimal mode of birth, a pregnant woman with an active monkeypox infection may choose to avoid vaginal delivery to reduce direct contact.

“If genital lesions are identified on a pregnant woman, then a cesarean birth will be recommended,” the authors wrote. “If a pregnant woman or person has suspected or confirmed monkeypox, a caesarean birth will be offered following discussion of the possible risk of neonatal infection, which may be serious.”

After giving birth, close contact can spread the virus as well. To minimize the risk, the authors recommend isolating the baby from family members who have confirmed or suspected monkeypox and carefully monitoring for infection.

Mothers with an active monkeypox infection should also avoid breastfeeding to lower the risk of spreading the virus to their newborn, the authors wrote. But to support breastfeeding after infection, mothers can express and discard milk until the isolation period has passed.

Pregnant women who become infected may also consider getting vaccinated, the authors wrote. Vaccination up to 14 days after exposure doesn’t prevent the disease but can reduce the severity of symptoms. In the current outbreak, public health organizations advised doctors to vaccinate contacts of confirmed cases, including pregnant people.

The data for monkeypox vaccine use in pregnant women is small, the authors wrote, including fewer than 300 women. In previous studies, no adverse outcomes were found. The vaccine is also considered safe for breastfeeding.

“The decision whether to have the vaccine in pregnancy should be a personal choice,” the authors wrote. “Pregnant women and people should be encouraged to discuss the risks and benefits of vaccination, including possible side effects, with a health care professional before making their final decision.”

A version of this article first appeared on Medscape.com.

Pregnant women with monkeypox will be advised to give birth by C-section to avoid infecting their baby during delivery, according to a new paper in Ultrasound in Obstetrics & Gynecology.

The risk of monkeypox infection remains low for the general public, the authors wrote, though cases continue to grow worldwide, particularly in the United Kingdom.

“We are aware infants and children are at greater risk of becoming seriously ill if they do catch monkeypox,” Edward Morris, MBBS, one of the authors and president of the Royal College of Obstetricians and Gynecologists, said in a statement.

“Therefore, to minimize the risk of a baby contracting the virus, we recommend health care professionals discuss the benefits and risks of having a cesarean birth with a pregnant woman or person who has or is suspected of having the virus,” he said.

Dr. Morris and colleagues pulled together existing evidence on monkeypox diagnosis, treatment, and recommended modes of birth for mothers and babies.

“The World Health Organization states there could be adverse consequences for pregnant women and babies if they become infected, including congenital monkeypox, miscarriage, or stillbirth, which is why we have provided clear guidance for health care professionals in this paper,” Dr. Morris said.

The monkeypox virus typically spreads through direct contact, droplets, or contaminated surfaces and objects. But some limited evidence shows that the virus can be passed from a mother to a baby via the placenta, which can lead to congenital monkeypox.

What’s more, mothers may be able to transmit the virus during or after birth. Although no evidence exists around the optimal mode of birth, a pregnant woman with an active monkeypox infection may choose to avoid vaginal delivery to reduce direct contact.

“If genital lesions are identified on a pregnant woman, then a cesarean birth will be recommended,” the authors wrote. “If a pregnant woman or person has suspected or confirmed monkeypox, a caesarean birth will be offered following discussion of the possible risk of neonatal infection, which may be serious.”

After giving birth, close contact can spread the virus as well. To minimize the risk, the authors recommend isolating the baby from family members who have confirmed or suspected monkeypox and carefully monitoring for infection.

Mothers with an active monkeypox infection should also avoid breastfeeding to lower the risk of spreading the virus to their newborn, the authors wrote. But to support breastfeeding after infection, mothers can express and discard milk until the isolation period has passed.

Pregnant women who become infected may also consider getting vaccinated, the authors wrote. Vaccination up to 14 days after exposure doesn’t prevent the disease but can reduce the severity of symptoms. In the current outbreak, public health organizations advised doctors to vaccinate contacts of confirmed cases, including pregnant people.

The data for monkeypox vaccine use in pregnant women is small, the authors wrote, including fewer than 300 women. In previous studies, no adverse outcomes were found. The vaccine is also considered safe for breastfeeding.

“The decision whether to have the vaccine in pregnancy should be a personal choice,” the authors wrote. “Pregnant women and people should be encouraged to discuss the risks and benefits of vaccination, including possible side effects, with a health care professional before making their final decision.”

A version of this article first appeared on Medscape.com.

Technical and procedural success rates for chronic total occlusion percutaneous coronary intervention (CTO PCI) have increased steadily over the past 6 years, with rates of in-hospital major adverse cardiac events (MACE) declining to the 2%-or-lower range in that time.

“CTO PCI technical and procedural success rates are high and continue to increase over time,” Spyridon Kostantinis, MD said in presenting updated results from the international PROGRESS-CTO registry at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

Courtesy Minneapolis Heart Institute Foundation

“The overall success rate increased from 81.6% in 2018 to 88.1% in 2021,” he added. The overall incidence of in-hospital MACE in that time was “an acceptable” 2.1% without significant changes over that period.

The analysis examined clinical, angiographic and procedural outcomes of 10,249 CTO PCIs performed on 10,019 patients from 63 centers in nine countries during 2016-2021. PROGRESS-CTO stands for Prospective Global Registry for the Study of Chronic Total Occlusion Intervention.

The target CTOs were highly complex, he said, with an average J-CTO (multicenter CTO registry in Japan) score of 2.4 ± 1.3 and PROGRESS-CTO score of 1.3 ± 1. The most common CTO target vessel was the right coronary artery (53%), followed by the left anterior descending artery (26%) and the circumflex artery (19%).

The registry also tracked how characteristics of the CTO PCI procedures themselves changed over time. “The septal and the epicardial collaterals were the most common collaterals used for retrograde crossing, with a decreasing trend for epicardial collaterals over time,” said Dr. Kostantinis, a research fellow at the Minneapolis Heart Institute.

Septal collateral use varied between 64% and 69% of cases from 2016 to 2021, but the share of epicardial collaterals declined from 35% to 22% in that time.

“Over time, the range of antegrade wiring as the final successfully crossing strategy increased from 46% in 2016 to 61% in 2021, with a decrease in antegrade dissection and re-entry (ADR) and no change in the retrograde approach,” Dr. Kostantinis said. The percentage of procedures using ADR as the final crossing strategy declined from 18% in 2016 to 12% in 2021, with the rate of retrograde crossings peaking at 21% in 2016 but leveling off to 18% or 19% in the subsequent years.

“An increasing use in the efficiency of antegrade wiring may reflect an improvement in guidewire retrograde crossing as well as the increasing operator expertise,” Dr. Kostantinis said.

The study also found that contrast volume, air kerma radiation dose, fluoroscopy time, and procedure time declined steadily over time. “The potential explanations for these are using new x-ray systems as well as the use of intravascular imaging,” Dr. Kostantinis said.

In 2020, the rates of technical and procedural success, as well as the number of overall procedures, declined from 2019, while MACE rates ticked upward that year, probably because of the COVID-19 pandemic, Dr. Kostantinis said.

“It is true that we noticed a rise in MACE rate from 1.6% in 2019 to 2.7% in 2020, but in 2021 that decreased again to 1.7%,” he said in an interview. “Another potential explanation is the higher angiographic complexity of CTOs treated during that year (2020) that resulted in more adverse events.”

Previous results from the PROGRESS-CTO registry reported the difference in MACE between 2019 and 2020 was significant (P  = .01). “So, yes, the difference between those 2 years is significant,” Dr. Kostantinis said. However, he noted, the overall trend was not significant, with a P value of .194.

The risk profile of CTO PCI has improved “slowly” over time, said Kirk N. Garratt, MD, but “it’s not yet were it needs to be.”

He added, “Undoubtedly we’ve learned that, without any question, one method for minimizing the risk is to concentrate these cases in the hands of those that do many of them.” As the number of procedures fell – an “embedded” pandemic impact –“I worry that it’s inevitable that complication rates will tick up a bit,” said Dr. Garratt, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del.

By the same token, he added, this situation with regard to CTOs “parallels what’s happening elsewhere in interventional medicine and medicine broadly; numbers are increasing and we’re busy again. In most domains we’re not as busy as we had been prepandemic, and time will allow us to catch up.”

PROGRESS-CTO has received funding from the Joseph F. and Mary M. Fleischhacker Foundation and the Abbott Northwestern Hospital Foundation Innovation Grant.

Dr. Kostantinis has no disclosures. Dr. Garratt is an advisory board member for Abbott.

Technical and procedural success rates for chronic total occlusion percutaneous coronary intervention (CTO PCI) have increased steadily over the past 6 years, with rates of in-hospital major adverse cardiac events (MACE) declining to the 2%-or-lower range in that time.

“CTO PCI technical and procedural success rates are high and continue to increase over time,” Spyridon Kostantinis, MD said in presenting updated results from the international PROGRESS-CTO registry at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

Courtesy Minneapolis Heart Institute Foundation

“The overall success rate increased from 81.6% in 2018 to 88.1% in 2021,” he added. The overall incidence of in-hospital MACE in that time was “an acceptable” 2.1% without significant changes over that period.

The analysis examined clinical, angiographic and procedural outcomes of 10,249 CTO PCIs performed on 10,019 patients from 63 centers in nine countries during 2016-2021. PROGRESS-CTO stands for Prospective Global Registry for the Study of Chronic Total Occlusion Intervention.

The target CTOs were highly complex, he said, with an average J-CTO (multicenter CTO registry in Japan) score of 2.4 ± 1.3 and PROGRESS-CTO score of 1.3 ± 1. The most common CTO target vessel was the right coronary artery (53%), followed by the left anterior descending artery (26%) and the circumflex artery (19%).

The registry also tracked how characteristics of the CTO PCI procedures themselves changed over time. “The septal and the epicardial collaterals were the most common collaterals used for retrograde crossing, with a decreasing trend for epicardial collaterals over time,” said Dr. Kostantinis, a research fellow at the Minneapolis Heart Institute.

Septal collateral use varied between 64% and 69% of cases from 2016 to 2021, but the share of epicardial collaterals declined from 35% to 22% in that time.

“Over time, the range of antegrade wiring as the final successfully crossing strategy increased from 46% in 2016 to 61% in 2021, with a decrease in antegrade dissection and re-entry (ADR) and no change in the retrograde approach,” Dr. Kostantinis said. The percentage of procedures using ADR as the final crossing strategy declined from 18% in 2016 to 12% in 2021, with the rate of retrograde crossings peaking at 21% in 2016 but leveling off to 18% or 19% in the subsequent years.

“An increasing use in the efficiency of antegrade wiring may reflect an improvement in guidewire retrograde crossing as well as the increasing operator expertise,” Dr. Kostantinis said.

The study also found that contrast volume, air kerma radiation dose, fluoroscopy time, and procedure time declined steadily over time. “The potential explanations for these are using new x-ray systems as well as the use of intravascular imaging,” Dr. Kostantinis said.

In 2020, the rates of technical and procedural success, as well as the number of overall procedures, declined from 2019, while MACE rates ticked upward that year, probably because of the COVID-19 pandemic, Dr. Kostantinis said.

“It is true that we noticed a rise in MACE rate from 1.6% in 2019 to 2.7% in 2020, but in 2021 that decreased again to 1.7%,” he said in an interview. “Another potential explanation is the higher angiographic complexity of CTOs treated during that year (2020) that resulted in more adverse events.”

Previous results from the PROGRESS-CTO registry reported the difference in MACE between 2019 and 2020 was significant (P  = .01). “So, yes, the difference between those 2 years is significant,” Dr. Kostantinis said. However, he noted, the overall trend was not significant, with a P value of .194.

The risk profile of CTO PCI has improved “slowly” over time, said Kirk N. Garratt, MD, but “it’s not yet were it needs to be.”

He added, “Undoubtedly we’ve learned that, without any question, one method for minimizing the risk is to concentrate these cases in the hands of those that do many of them.” As the number of procedures fell – an “embedded” pandemic impact –“I worry that it’s inevitable that complication rates will tick up a bit,” said Dr. Garratt, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del.

By the same token, he added, this situation with regard to CTOs “parallels what’s happening elsewhere in interventional medicine and medicine broadly; numbers are increasing and we’re busy again. In most domains we’re not as busy as we had been prepandemic, and time will allow us to catch up.”

PROGRESS-CTO has received funding from the Joseph F. and Mary M. Fleischhacker Foundation and the Abbott Northwestern Hospital Foundation Innovation Grant.

Dr. Kostantinis has no disclosures. Dr. Garratt is an advisory board member for Abbott.

Technical and procedural success rates for chronic total occlusion percutaneous coronary intervention (CTO PCI) have increased steadily over the past 6 years, with rates of in-hospital major adverse cardiac events (MACE) declining to the 2%-or-lower range in that time.

“CTO PCI technical and procedural success rates are high and continue to increase over time,” Spyridon Kostantinis, MD said in presenting updated results from the international PROGRESS-CTO registry at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

Courtesy Minneapolis Heart Institute Foundation

“The overall success rate increased from 81.6% in 2018 to 88.1% in 2021,” he added. The overall incidence of in-hospital MACE in that time was “an acceptable” 2.1% without significant changes over that period.

The analysis examined clinical, angiographic and procedural outcomes of 10,249 CTO PCIs performed on 10,019 patients from 63 centers in nine countries during 2016-2021. PROGRESS-CTO stands for Prospective Global Registry for the Study of Chronic Total Occlusion Intervention.

The target CTOs were highly complex, he said, with an average J-CTO (multicenter CTO registry in Japan) score of 2.4 ± 1.3 and PROGRESS-CTO score of 1.3 ± 1. The most common CTO target vessel was the right coronary artery (53%), followed by the left anterior descending artery (26%) and the circumflex artery (19%).

The registry also tracked how characteristics of the CTO PCI procedures themselves changed over time. “The septal and the epicardial collaterals were the most common collaterals used for retrograde crossing, with a decreasing trend for epicardial collaterals over time,” said Dr. Kostantinis, a research fellow at the Minneapolis Heart Institute.

Septal collateral use varied between 64% and 69% of cases from 2016 to 2021, but the share of epicardial collaterals declined from 35% to 22% in that time.

“Over time, the range of antegrade wiring as the final successfully crossing strategy increased from 46% in 2016 to 61% in 2021, with a decrease in antegrade dissection and re-entry (ADR) and no change in the retrograde approach,” Dr. Kostantinis said. The percentage of procedures using ADR as the final crossing strategy declined from 18% in 2016 to 12% in 2021, with the rate of retrograde crossings peaking at 21% in 2016 but leveling off to 18% or 19% in the subsequent years.

“An increasing use in the efficiency of antegrade wiring may reflect an improvement in guidewire retrograde crossing as well as the increasing operator expertise,” Dr. Kostantinis said.

The study also found that contrast volume, air kerma radiation dose, fluoroscopy time, and procedure time declined steadily over time. “The potential explanations for these are using new x-ray systems as well as the use of intravascular imaging,” Dr. Kostantinis said.

In 2020, the rates of technical and procedural success, as well as the number of overall procedures, declined from 2019, while MACE rates ticked upward that year, probably because of the COVID-19 pandemic, Dr. Kostantinis said.

“It is true that we noticed a rise in MACE rate from 1.6% in 2019 to 2.7% in 2020, but in 2021 that decreased again to 1.7%,” he said in an interview. “Another potential explanation is the higher angiographic complexity of CTOs treated during that year (2020) that resulted in more adverse events.”

Previous results from the PROGRESS-CTO registry reported the difference in MACE between 2019 and 2020 was significant (P  = .01). “So, yes, the difference between those 2 years is significant,” Dr. Kostantinis said. However, he noted, the overall trend was not significant, with a P value of .194.

The risk profile of CTO PCI has improved “slowly” over time, said Kirk N. Garratt, MD, but “it’s not yet were it needs to be.”

He added, “Undoubtedly we’ve learned that, without any question, one method for minimizing the risk is to concentrate these cases in the hands of those that do many of them.” As the number of procedures fell – an “embedded” pandemic impact –“I worry that it’s inevitable that complication rates will tick up a bit,” said Dr. Garratt, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del.

By the same token, he added, this situation with regard to CTOs “parallels what’s happening elsewhere in interventional medicine and medicine broadly; numbers are increasing and we’re busy again. In most domains we’re not as busy as we had been prepandemic, and time will allow us to catch up.”

PROGRESS-CTO has received funding from the Joseph F. and Mary M. Fleischhacker Foundation and the Abbott Northwestern Hospital Foundation Innovation Grant.

Dr. Kostantinis has no disclosures. Dr. Garratt is an advisory board member for Abbott.

COVID-19 infection during pregnancy has been linked to a small but significant effect on infant neurodevelopment, suggests a small-scale analysis that points to the need for further study and monitoring during pregnancy.

The study included 24 pregnant women, half of whom had COVID-19 during pregnancy, and their offspring. It showed impairments at 6 weeks of age on the social interactive dimension of a neonatal assessment.

“Not all babies born to mothers infected with COVID show neurodevelopmental differences, but our data show that their risk is increased in comparison to those not exposed to COVID in the womb. We need a bigger study to confirm the exact extent of the difference,” said lead researcher Rosa Ayesa Arriola, PhD, Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain, in a release.

The findings were presented at the virtual European Psychiatric Association 2022 Congress.
 

Differing responses to cuddling

Coauthor Águeda Castro Quintas, PhD student, Network Centre for Biomedical Research in Mental Health, University of Barcelona, explained that the tests showed the children born to mothers who had COVID-19 during pregnancy reacted “slightly differently to being held, or cuddled.”

“We need to note that these are preliminary results, but this is part of a project following a larger sample of 100 mothers and their babies,” she added. The authors plan to compare their results with those from a similar study.

The group will also monitor infant language and motor development aged between 18 and 42 months.

“This is an ongoing project, and we are at an early stage,” Ms. Castro Quintas said. “We don’t know if these effects will result in any longer-term issues,” but longer-term observation “may help us understand this.”

“Of course, in babies who are so young, there are several things we just can’t measure, such as language skills or cognition,” added coinvestigator Nerea San Martín González, department of evolutionary biology, ecology and environmental sciences, University of Barcelona.

While emphasizing the need for larger sample sizes, she said that “in the meantime, we need to stress the importance of medical monitoring to facilitate a healthy pregnancy.”

The researchers note that the consequences of the COVID-19 pandemic for the newborns of affected mothers remain “unknown.”

However, previous studies of other infections during pregnancy suggest that offspring could be “especially vulnerable,”as the pathophysiological mechanisms of the infection, such as cytokine storms and microcoagulation, “could clearly compromise fetal neurodevelopment.”

To investigate further, they examined the neurodevelopment of infants born both immediately before and during the COVID-19 pandemic, from 2017 to 2021.

Twenty-one women who had COVID-19 during pregnancy were matched with 21 healthy controls. They were studied both during pregnancy and in the postpartum period, completing hormonal and other biochemical tests, salivary tests, movement assessments, and psychological questionnaires, adjusted for various factors.

The team also administered the Brazelton Neonatal Behavioural Assessment Scale (NBAS) to the offspring at 6 weeks of age to evaluate neurologic, social, and behavioral aspects of function.

“We have been especially sensitive in how we have conducted these tests,” said Ms. Castro Quintas. “Each mother and baby were closely examined by clinicians with expert training in the field and in the tests.”

Among those offspring exposed to COVID-19 during pregnancy, there was a significant decrease in scores on the social interactive dimension of the NBAS, particularly if infection occurred before week 20 of gestation.

Other NBAS subscales were not associated with maternal COVID-19 during pregnancy.
 

More research needed

Commenting on the findings, Livio Provenzi, PhD, a psychologist and researcher in developmental psychobiology at the University of Pavia (Italy), noted there is a “great need” to study the direct and indirect effect of the COVID-19 pandemic on parents and their children. “Pregnancy is a period of life which shapes much of our subsequent development, and exposure to adversity in pregnancy can leave long-lasting biological footprints.”

Dr. Provenzi, who was not involved in the study, added in the release that the findings reinforce “evidence of epigenetic alterations in infants born from mothers exposed to pandemic-related stress during pregnancy.

“It shows we need more large-scale, international research to allow us to understand the developmental effects of this health emergency and to deliver better quality of care to parents and infants.”

The study was funded by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III through the University of Barcelona multicenter project and the Government of Cantabria. No relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

COVID-19 infection during pregnancy has been linked to a small but significant effect on infant neurodevelopment, suggests a small-scale analysis that points to the need for further study and monitoring during pregnancy.

The study included 24 pregnant women, half of whom had COVID-19 during pregnancy, and their offspring. It showed impairments at 6 weeks of age on the social interactive dimension of a neonatal assessment.

“Not all babies born to mothers infected with COVID show neurodevelopmental differences, but our data show that their risk is increased in comparison to those not exposed to COVID in the womb. We need a bigger study to confirm the exact extent of the difference,” said lead researcher Rosa Ayesa Arriola, PhD, Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain, in a release.

The findings were presented at the virtual European Psychiatric Association 2022 Congress.
 

Differing responses to cuddling

Coauthor Águeda Castro Quintas, PhD student, Network Centre for Biomedical Research in Mental Health, University of Barcelona, explained that the tests showed the children born to mothers who had COVID-19 during pregnancy reacted “slightly differently to being held, or cuddled.”

“We need to note that these are preliminary results, but this is part of a project following a larger sample of 100 mothers and their babies,” she added. The authors plan to compare their results with those from a similar study.

The group will also monitor infant language and motor development aged between 18 and 42 months.

“This is an ongoing project, and we are at an early stage,” Ms. Castro Quintas said. “We don’t know if these effects will result in any longer-term issues,” but longer-term observation “may help us understand this.”

“Of course, in babies who are so young, there are several things we just can’t measure, such as language skills or cognition,” added coinvestigator Nerea San Martín González, department of evolutionary biology, ecology and environmental sciences, University of Barcelona.

While emphasizing the need for larger sample sizes, she said that “in the meantime, we need to stress the importance of medical monitoring to facilitate a healthy pregnancy.”

The researchers note that the consequences of the COVID-19 pandemic for the newborns of affected mothers remain “unknown.”

However, previous studies of other infections during pregnancy suggest that offspring could be “especially vulnerable,”as the pathophysiological mechanisms of the infection, such as cytokine storms and microcoagulation, “could clearly compromise fetal neurodevelopment.”

To investigate further, they examined the neurodevelopment of infants born both immediately before and during the COVID-19 pandemic, from 2017 to 2021.

Twenty-one women who had COVID-19 during pregnancy were matched with 21 healthy controls. They were studied both during pregnancy and in the postpartum period, completing hormonal and other biochemical tests, salivary tests, movement assessments, and psychological questionnaires, adjusted for various factors.

The team also administered the Brazelton Neonatal Behavioural Assessment Scale (NBAS) to the offspring at 6 weeks of age to evaluate neurologic, social, and behavioral aspects of function.

“We have been especially sensitive in how we have conducted these tests,” said Ms. Castro Quintas. “Each mother and baby were closely examined by clinicians with expert training in the field and in the tests.”

Among those offspring exposed to COVID-19 during pregnancy, there was a significant decrease in scores on the social interactive dimension of the NBAS, particularly if infection occurred before week 20 of gestation.

Other NBAS subscales were not associated with maternal COVID-19 during pregnancy.
 

More research needed

Commenting on the findings, Livio Provenzi, PhD, a psychologist and researcher in developmental psychobiology at the University of Pavia (Italy), noted there is a “great need” to study the direct and indirect effect of the COVID-19 pandemic on parents and their children. “Pregnancy is a period of life which shapes much of our subsequent development, and exposure to adversity in pregnancy can leave long-lasting biological footprints.”

Dr. Provenzi, who was not involved in the study, added in the release that the findings reinforce “evidence of epigenetic alterations in infants born from mothers exposed to pandemic-related stress during pregnancy.

“It shows we need more large-scale, international research to allow us to understand the developmental effects of this health emergency and to deliver better quality of care to parents and infants.”

The study was funded by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III through the University of Barcelona multicenter project and the Government of Cantabria. No relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

COVID-19 infection during pregnancy has been linked to a small but significant effect on infant neurodevelopment, suggests a small-scale analysis that points to the need for further study and monitoring during pregnancy.

The study included 24 pregnant women, half of whom had COVID-19 during pregnancy, and their offspring. It showed impairments at 6 weeks of age on the social interactive dimension of a neonatal assessment.

“Not all babies born to mothers infected with COVID show neurodevelopmental differences, but our data show that their risk is increased in comparison to those not exposed to COVID in the womb. We need a bigger study to confirm the exact extent of the difference,” said lead researcher Rosa Ayesa Arriola, PhD, Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain, in a release.

The findings were presented at the virtual European Psychiatric Association 2022 Congress.
 

Differing responses to cuddling

Coauthor Águeda Castro Quintas, PhD student, Network Centre for Biomedical Research in Mental Health, University of Barcelona, explained that the tests showed the children born to mothers who had COVID-19 during pregnancy reacted “slightly differently to being held, or cuddled.”

“We need to note that these are preliminary results, but this is part of a project following a larger sample of 100 mothers and their babies,” she added. The authors plan to compare their results with those from a similar study.

The group will also monitor infant language and motor development aged between 18 and 42 months.

“This is an ongoing project, and we are at an early stage,” Ms. Castro Quintas said. “We don’t know if these effects will result in any longer-term issues,” but longer-term observation “may help us understand this.”

“Of course, in babies who are so young, there are several things we just can’t measure, such as language skills or cognition,” added coinvestigator Nerea San Martín González, department of evolutionary biology, ecology and environmental sciences, University of Barcelona.

While emphasizing the need for larger sample sizes, she said that “in the meantime, we need to stress the importance of medical monitoring to facilitate a healthy pregnancy.”

The researchers note that the consequences of the COVID-19 pandemic for the newborns of affected mothers remain “unknown.”

However, previous studies of other infections during pregnancy suggest that offspring could be “especially vulnerable,”as the pathophysiological mechanisms of the infection, such as cytokine storms and microcoagulation, “could clearly compromise fetal neurodevelopment.”

To investigate further, they examined the neurodevelopment of infants born both immediately before and during the COVID-19 pandemic, from 2017 to 2021.

Twenty-one women who had COVID-19 during pregnancy were matched with 21 healthy controls. They were studied both during pregnancy and in the postpartum period, completing hormonal and other biochemical tests, salivary tests, movement assessments, and psychological questionnaires, adjusted for various factors.

The team also administered the Brazelton Neonatal Behavioural Assessment Scale (NBAS) to the offspring at 6 weeks of age to evaluate neurologic, social, and behavioral aspects of function.

“We have been especially sensitive in how we have conducted these tests,” said Ms. Castro Quintas. “Each mother and baby were closely examined by clinicians with expert training in the field and in the tests.”

Among those offspring exposed to COVID-19 during pregnancy, there was a significant decrease in scores on the social interactive dimension of the NBAS, particularly if infection occurred before week 20 of gestation.

Other NBAS subscales were not associated with maternal COVID-19 during pregnancy.
 

More research needed

Commenting on the findings, Livio Provenzi, PhD, a psychologist and researcher in developmental psychobiology at the University of Pavia (Italy), noted there is a “great need” to study the direct and indirect effect of the COVID-19 pandemic on parents and their children. “Pregnancy is a period of life which shapes much of our subsequent development, and exposure to adversity in pregnancy can leave long-lasting biological footprints.”

Dr. Provenzi, who was not involved in the study, added in the release that the findings reinforce “evidence of epigenetic alterations in infants born from mothers exposed to pandemic-related stress during pregnancy.

“It shows we need more large-scale, international research to allow us to understand the developmental effects of this health emergency and to deliver better quality of care to parents and infants.”

The study was funded by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III through the University of Barcelona multicenter project and the Government of Cantabria. No relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

Four common motor abnormalities in schizophrenia patients were associated with at least one poor functional outcome, based on data from 156 individuals.

Approximately half of adults with schizophrenia suffer from motor abnormalities that may impair their ability to work and decrease their quality of life, wrote Niluja Nadesalingam, MD, of the University of Bern, Switzerland, and colleagues. “Although previous reports show strong associations between single movement abnormalities and global as well as social functioning, we still struggle to understand the contribution of various motor domains,” they said.

The impact of these abnormalities on social and global functioning and on functional capacity remains unclear, but the researchers proposed that motor abnormalities would be associated with worse functional outcomes in schizophrenia patients.

In a study published in Comprehensive Psychiatry, the researchers identified patients with diagnosed schizophrenia spectrum disorders who were treated on an inpatient or outpatient basis at a single center. They collected data on five motor abnormalities: parkinsonism, catatonia, dyskinesia, neurological soft signs (NSS), and psychomotor slowing (PS). They assessed functional outcomes using the Global Assessment of Functioning (GAF), the Social and Occupational Functioning Assessment Scale (SOFAS), and the UCSD Performance-Based Skills Assessment (UPSA-B). The average age of the participants was 37.9 years and 88 of the 156 were male. The average duration of illness was 12.5 years.

Overall, patients with catatonia and parkinsonism scored significantly lower on GAF and SOFAS scale compared to those without catatonia and parkinsonism (P < .035 and P < .027, respectively).

No significant differences in functional outcomes appeared between patients with and without dyskinesia.

However, significant negative correlations were identified for parkinsonism and PS with GAF, SOFAS, and UPSA-B (P < .036 for all). “Our study further found that parkinsonism and psychomotor slowing also impair the functional capacity of patients,” which may be influenced by factors including deficits in social interaction and cognitive impairment, the researchers said.

Overall, the study findings demonstrate that motor abnormalities in patients with schizophrenia are strongly associated with poor functional outcomes, and the stronger the motor impairment, the worse the global and social functioning, the researchers said.

As for potential pathways, “motor abnormalities are readily observable signs, allowing laypersons to perceive subjects with schizophrenia as somebody with severe mental illness. Thus, motor abnormalities might lead to stigmatization of patients suffering from schizophrenia,” they wrote in their discussion.

The researchers emphasized the need to explore alternative treatment options that might improve motor abnormalities, such as transcranial magnetic stimulation, given the potential of antipsychotic medications to introduce additional motor abnormalities.

The study findings were limited by several factors including the potential for missed confounding variables, the small number of patients with dyskinesia, and the inability to deduce the course of illness because most of the patients were in psychotic episodes, the researchers noted.

However, the results suggest that specific motor abnormalities are associated with poor global and social functioning, and with reduced functional capacity, in adults with schizophrenia, the researchers said. “Future studies need to test whether amelioration of motor abnormalities may improve community functioning,” they concluded.

The study was supported by the Swiss National Science Foundation, the Bangerter Rhyner Foundation, and the Adrian and Simone Frutiger Foundation. Lead author Dr. Nadesalingam had no financial conflicts to disclose.

Four common motor abnormalities in schizophrenia patients were associated with at least one poor functional outcome, based on data from 156 individuals.

Approximately half of adults with schizophrenia suffer from motor abnormalities that may impair their ability to work and decrease their quality of life, wrote Niluja Nadesalingam, MD, of the University of Bern, Switzerland, and colleagues. “Although previous reports show strong associations between single movement abnormalities and global as well as social functioning, we still struggle to understand the contribution of various motor domains,” they said.

The impact of these abnormalities on social and global functioning and on functional capacity remains unclear, but the researchers proposed that motor abnormalities would be associated with worse functional outcomes in schizophrenia patients.

In a study published in Comprehensive Psychiatry, the researchers identified patients with diagnosed schizophrenia spectrum disorders who were treated on an inpatient or outpatient basis at a single center. They collected data on five motor abnormalities: parkinsonism, catatonia, dyskinesia, neurological soft signs (NSS), and psychomotor slowing (PS). They assessed functional outcomes using the Global Assessment of Functioning (GAF), the Social and Occupational Functioning Assessment Scale (SOFAS), and the UCSD Performance-Based Skills Assessment (UPSA-B). The average age of the participants was 37.9 years and 88 of the 156 were male. The average duration of illness was 12.5 years.

Overall, patients with catatonia and parkinsonism scored significantly lower on GAF and SOFAS scale compared to those without catatonia and parkinsonism (P < .035 and P < .027, respectively).

No significant differences in functional outcomes appeared between patients with and without dyskinesia.

However, significant negative correlations were identified for parkinsonism and PS with GAF, SOFAS, and UPSA-B (P < .036 for all). “Our study further found that parkinsonism and psychomotor slowing also impair the functional capacity of patients,” which may be influenced by factors including deficits in social interaction and cognitive impairment, the researchers said.

Overall, the study findings demonstrate that motor abnormalities in patients with schizophrenia are strongly associated with poor functional outcomes, and the stronger the motor impairment, the worse the global and social functioning, the researchers said.

As for potential pathways, “motor abnormalities are readily observable signs, allowing laypersons to perceive subjects with schizophrenia as somebody with severe mental illness. Thus, motor abnormalities might lead to stigmatization of patients suffering from schizophrenia,” they wrote in their discussion.

The researchers emphasized the need to explore alternative treatment options that might improve motor abnormalities, such as transcranial magnetic stimulation, given the potential of antipsychotic medications to introduce additional motor abnormalities.

The study findings were limited by several factors including the potential for missed confounding variables, the small number of patients with dyskinesia, and the inability to deduce the course of illness because most of the patients were in psychotic episodes, the researchers noted.

However, the results suggest that specific motor abnormalities are associated with poor global and social functioning, and with reduced functional capacity, in adults with schizophrenia, the researchers said. “Future studies need to test whether amelioration of motor abnormalities may improve community functioning,” they concluded.

The study was supported by the Swiss National Science Foundation, the Bangerter Rhyner Foundation, and the Adrian and Simone Frutiger Foundation. Lead author Dr. Nadesalingam had no financial conflicts to disclose.

Four common motor abnormalities in schizophrenia patients were associated with at least one poor functional outcome, based on data from 156 individuals.

Approximately half of adults with schizophrenia suffer from motor abnormalities that may impair their ability to work and decrease their quality of life, wrote Niluja Nadesalingam, MD, of the University of Bern, Switzerland, and colleagues. “Although previous reports show strong associations between single movement abnormalities and global as well as social functioning, we still struggle to understand the contribution of various motor domains,” they said.

The impact of these abnormalities on social and global functioning and on functional capacity remains unclear, but the researchers proposed that motor abnormalities would be associated with worse functional outcomes in schizophrenia patients.

In a study published in Comprehensive Psychiatry, the researchers identified patients with diagnosed schizophrenia spectrum disorders who were treated on an inpatient or outpatient basis at a single center. They collected data on five motor abnormalities: parkinsonism, catatonia, dyskinesia, neurological soft signs (NSS), and psychomotor slowing (PS). They assessed functional outcomes using the Global Assessment of Functioning (GAF), the Social and Occupational Functioning Assessment Scale (SOFAS), and the UCSD Performance-Based Skills Assessment (UPSA-B). The average age of the participants was 37.9 years and 88 of the 156 were male. The average duration of illness was 12.5 years.

Overall, patients with catatonia and parkinsonism scored significantly lower on GAF and SOFAS scale compared to those without catatonia and parkinsonism (P < .035 and P < .027, respectively).

No significant differences in functional outcomes appeared between patients with and without dyskinesia.

However, significant negative correlations were identified for parkinsonism and PS with GAF, SOFAS, and UPSA-B (P < .036 for all). “Our study further found that parkinsonism and psychomotor slowing also impair the functional capacity of patients,” which may be influenced by factors including deficits in social interaction and cognitive impairment, the researchers said.

Overall, the study findings demonstrate that motor abnormalities in patients with schizophrenia are strongly associated with poor functional outcomes, and the stronger the motor impairment, the worse the global and social functioning, the researchers said.

As for potential pathways, “motor abnormalities are readily observable signs, allowing laypersons to perceive subjects with schizophrenia as somebody with severe mental illness. Thus, motor abnormalities might lead to stigmatization of patients suffering from schizophrenia,” they wrote in their discussion.

The researchers emphasized the need to explore alternative treatment options that might improve motor abnormalities, such as transcranial magnetic stimulation, given the potential of antipsychotic medications to introduce additional motor abnormalities.

The study findings were limited by several factors including the potential for missed confounding variables, the small number of patients with dyskinesia, and the inability to deduce the course of illness because most of the patients were in psychotic episodes, the researchers noted.

However, the results suggest that specific motor abnormalities are associated with poor global and social functioning, and with reduced functional capacity, in adults with schizophrenia, the researchers said. “Future studies need to test whether amelioration of motor abnormalities may improve community functioning,” they concluded.

The study was supported by the Swiss National Science Foundation, the Bangerter Rhyner Foundation, and the Adrian and Simone Frutiger Foundation. Lead author Dr. Nadesalingam had no financial conflicts to disclose.